title: Distinct roles of DMAP1 in mouse development.
abstract: DMAP1 (DNMT1-associated protein 1) is a member of the TIP60-p400 complex that maintains embryonic stem (ES) cell pluripotency and a complex containing the somatic form of DNA methyltransferase 1 (DNMT1s). DMAP1 interacts with DNMT1s through a domain that is absent in Dnmt1(V)(/)(V) mice expressing just the oocyte form (DNMT1o). A Dmap1-null allele was generated to study the role of DMAP1 in development. Consistent with the phenotypes of loss of other members of the TIP60-p400 complex, Dmap1(-/-) mice died during preimplantation in both Dnmt1(+/+) and Dnmt1(V)(/)(V) backgrounds. Unexpectedly, in the Dnmt1(V)(/)(V) background, Dmap1(+/-) parents produced mainly Dmap1(+/-) mice. Most Dmap1(+/+) progeny died during midgestation, with loss of DNA methylation on imprinted genes, suggesting that DMAP1 influences maintenance methylation mediated by DNMT1o. In this regard, a DMAP1-DNMT1o complex was detected in ES cells when DNMT1o was stably expressed but not when transiently expressed, indicating a novel interaction between DMAP1 and DNMT1o. These results suggest that DMAP1-DNMT1s and DMAP1-DNMT1o interactions are essential for normal development and that DMAP1-DNMT1o complexes are not readily formed in the embryo. Therefore, DMAP1 mediates distinct preimplantation epigenetic reprogramming processes: TIP60-p400 nucleosome remodeling and DNMT1 maintenance methylation.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
authors.forename: K Naga
authors.initials: KN
authors.lastname: Mohan
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: J Richard
authors.initials: JR
authors.lastname: Chaillet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000378:metabolism; D017353:Gene Deletion; D018392:Genomic Imprinting; D006720:Homozygote; D051379:Mice / Q000235:genetics / Q000254:growth & development*; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C485852:Dmap1 protein, mouse; D012097:Repressor Proteins